Early detection of Alzheimer’s disease

Susan Landau

Helen Wills Neuroscience Institute University of California, Berkeley

Lawrence Berkeley National Lab

Definitions

Dementia

A global, progressive loss of cognitive ability that ultimately impairs independent function

Alzheimer’s disease

The most common cause of dementia

Begins with subtle memory loss

Characteristic brain pathology

Risk Factors/Protective Factors

Increased Risk

Age

Genetics/family history

Head Injury

Decreased Risk

Education

Cognitive Engagement

Physical Exercise

Neuropathology of Alzheimer’s disease:Neuritic Plaques (amyloid) and

Neurofibrillary Tangles (tau)

amyloid (A )b plaque

neuro-fibrillary tangle(tau)

Amyloid Imaging with Positron Emission Tomography (PET)

PET Imaging

Amyloid Plaques

Fibrillar A

Amyloid Imaging with Positron Emission Tomography (PET)

PET Imaging

Fibrillar A

Alzheimer’s Disease

Normal Aging (Amyloid Negative)

Normal Aging (Amyloid Positive)

Amyloid PET Imaging in Aging

30% of normal older people are amyloid

positive

Amyloid is associated with cognitive decline over timeC

og

nit

ive

fun

ctio

n (

wo

rse

)

Individuals without amyloid

Co

gn

itiv

e fu

nct

ion

(w

ors

e

)

Time (years)

Individuals with amyloid

Lifestyle factors and Alzheimer’s disease risk

Lifestyle practicesCognitive, physical, social, occupational engagement

Improved cognitive functionDecreased AD riskSlower decline

Less amyloid ?

Lifetime cognitive activity and amyloid

Landau et al. Arch Neurol 2012

Amyl

oid

depo

sitio

n

Brain atrophy in Alzheimer’s Disease

Alzheimer’sDisease

(Hippocampal Atrophy)

Normal

Mild Cognitive Impairment

Hippocampus (involved in

memory function) is particularly

affected in AD

FDG-PET: Hypometabolism in Alzheimer’s vs Normal Aging

neural function

atrophy

The Amyloid Hypothesis of Alzheimer’s Disease

Amyloid

Cognitive DeclineandDementia

Early detection of amyloid

Amyloid PET imaging is an important tool in research and clinical trials -- but is currently not appropriate for routine clinical screening in cognitively normal people

Amyloid is linked to future cognitive decline, but :

Decline may occur >10 yrs after amyloid appears

Some individuals may not decline

Interventions or preventative treatment may only be effective early, since loss of cognitive and neural function may be irreversible

Resources and volunteer opportunities

• Alzheimer’s Disease Neuroimaging Initiative (ADNI)• National Institute on Aging

Thank you

Michael Weiner

Bob KoeppeDanielle HarveyLaurel BeckettLeslie ShawJohn TrojanowskiClifford JackChester MathisAndrew SaykinNorman Foster

Ronald PetersenPaul AisenMichael DonohueAnthony GamstArt TogaKaren CrawfordEric ReimanKewei Chen

Alzheimer’s Disease Neuroimaging Initiative

University of California, Berkeley

William JagustElizabeth MorminoHwamee Oh

Gil RabinoviciShawn Marks

Robert WilsonADNI participants and staffAvid Radiopharmaceuticals